Tthe role of perturbations in mitochondrial biogenesis in the development and progression of complications of diabetes in the heart and skeletal is being explored using both cellular models and genetically modified mouse models. Candidate proteins identified that may modulate the mitochondrial biogenesis program in diabetes have been identified and these are being characterized via functional genomics to evaluate their role in the development of mitochondrial dysfunction in diabetes. The proteins that are being investigated modulate mitochondrial biology via the modification of lysine residues of mitochondrial proteins the target regulatory proteins modulating these post-translational modifications being explored include acetyl-transferases, deacetylases and ubiquitin ligases. Translational studies are being performed to evaluate whether these experimental findings are valid in the human condition.